The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.
T cells in multiple myeloma display features of exhaustion and senescence at the tumor site
Open accessAbstract
BACKGROUND: Multiple myeloma is an incurable plasma cell malignancy that is mostly restricted to the bone marrow. Cancer-induced dysfunction of cytotoxic T cells at the tumor site may be responsible for immune evasion and therapeutical failure of immunotherapies. Therefore, enhanced knowledge about the actual status of T cells in myeloma bone marrow is urgently needed. Here, we assessed the expression of inhibitory molecules PD-1, CTLA-4, 2B4, CD160, senescence marker CD57, and CD28 on T cells of naive and treated myeloma patients in the bone marrow and peripheral blood and collected data on T cell subset distribution in both compartments. In addition, T cell function concerning proliferation and expression of T-bet, IL-2, IFNγ, and CD107a was investigated after in vitro stimulation by CD3/CD28. Finally, data was compared to healthy, age-matched donor T cells from both compartments. METHODS: H-thymidine incorporation. Statistical analyses were performed utilizing unpaired T test and Mann-Whitney U test. RESULTS: We observed enhanced T cell exhaustion and senescence especially at the tumor site. CD8+ T cells expressed several molecules associated with T cell exhaustion (PD-1, CTLA-4, 2B4, CD160) and T cell senescence (CD57, lack of CD28). This phenotype was associated with lower proliferative capacity and impaired function. Despite a high expression of the transcription factor T-bet, CD8+ T cells from the tumor site failed to produce IFNγ after CD3/CD28 in vitro restimulation and displayed a reduced ability to degranulate in response to T cell stimuli. Notably, the percentage of senescent CD57+CD28- CD8+ T cells was significantly lower in treated myeloma patients when compared to untreated patients. CONCLUSIONS: T cells from the bone marrow of myeloma patients were more severely impaired than peripheral T cells. While our data suggest that terminally differentiated cells are preferentially deleted by therapy, immune-checkpoint molecules were still present on T cells supporting the potential of checkpoint inhibitors to reactivate T cells in myeloma patients in combination therapies. However, additional avenues to restore anti-myeloma T cell responses are urgently needed.
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Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review
Wanchoo, R., Karam, S., Uppal, N. N., Barta, V. S., Deray, G., Devoe, C., Launay-Vacher, V., Jhaveri, K. D., & on behalf of Cancer and Kidney International Network Workgroup on Immune Checkpoint Inhibitors (2017) · American Journal of Nephrology · doi:10.1159/000455014 · Cited by 15,256
PD-1 blockade induces responses by inhibiting adaptive immune resistance
Tumeh, P. C., Harview, C. L., Yearley, J. H., Shintaku, I. P., Taylor, E. J. M., Robert, L., Chmielowski, B., Spasic, M., Henry, G., Ciobanu, V., et al. (2014) · Nature · doi:10.1038/nature13954 · Cited by 6,609
Molecular and cellular insights into T cell exhaustion
Wherry, E. J., & Kurachi, M. (2015) · Nature Reviews Immunology · doi:10.1038/nri3862 · Cited by 4,652
Restoring function in exhausted CD8 T cells during chronic viral infection
Barber, D. L., Wherry, E. J., Masopust, D., Zhu, B., Allison, J. P., Sharpe, A. H., Freeman, G. J., & Ahmed, R. (2006) · Nature · doi:10.1038/nature04444 · Cited by 3,986
PD-1 Blockade with Nivolumab in Relapsed or Refractory Hodgkin's Lymphoma
Ansell, S. M., Lesokhin, A. M., Borrello, I., Halwani, A., Scott, E. C., Gutierrez, M., Schuster, S. J., Millenson, M. M., Cattry, D., Freeman, G. J., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1411087 · Cited by 3,560
Nivolumab and ipilimumab versus ipilimumab in untreated melanoma
Postow, M. A., Chesney, J., Pavlick, A. C., Robert, C., Grossmann, K., McDermott, D., Linette, G. P., Meyer, N., Giguere, J. K., Agarwala, S. S., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1414428 · Cited by 2,781
MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer
Powles, T., Eder, J. P., Fine, G. D., Braiteh, F. S., Loriot, Y., Cruz, C., Bellmunt, J., Burris, H. A., Petrylak, D. P., Teng, S.-L., et al. (2014) · Nature · doi:10.1038/nature13904 · Cited by 2,381
Blackburn, S. D., Shin, H., Haining, W. N., Zou, T., Workman, C. J., Polley, A., Betts, M. R., Freeman, G. J., Vignali, D. A. A., & Wherry, E. J. (2009) · Nature Immunology · doi:10.1038/ni.1679 · Cited by 2,062
Joshi, N. S., Cui, W., Chandele, A., Lee, H. K., Urso, D. R., Hagman, J., Gapin, L., & Kaech, S. M. (2007) · Immunity · doi:10.1016/j.immuni.2007.07.010 · Cited by 1,861
Betts, M. R., Brenchley, J. M., Price, D. A., De Rosa, S. C., Douek, D. C., Roederer, M., & Koup, R. A. (2003) · Journal of Immunological Methods · doi:10.1016/s0022-1759(03)00265-5 · Cited by 1,587
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The Role of Tumor Microenvironment in Multiple Myeloma Development and Progression
García-Ortiz, A., Rodríguez-García, Y., Encinas, J., Maroto-Martín, E., Castellano, E., Teixidó, J., & Martínez-López, J. (2021) · Cancers · doi:10.3390/cancers13020217 · Cited by 238
Tremblay-LeMay, R., Rastgoo, N., & Chang, H. (2018) · Journal of Hematology & Oncology · doi:10.1186/s13045-018-0589-1 · Cited by 69
Understanding the Role of T-Cells in the Antimyeloma Effect of Immunomodulatory Drugs
D'Souza, C., Prince, H. M., & Neeson, P. J. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.632399 · Cited by 52
Yao, L., Jayasinghe, R. G., Lee, B. H., Bhasin, S. S., Pilcher, W., Doxie, D. B., Gonzalez-Kozlova, E., Dasari, S., Fiala, M. A., Pita-Juarez, Y., et al. (2022) · Cancer Research Communications · doi:10.1158/2767-9764.crc-22-0022 · Cited by 45
Metadata
- Authors
- Zelle-Rieser, C., Thangavadivel, S., Biedermann, R., Brunner, A., Stoitzner, P., Willenbacher, E., Greil, R., & Jöhrer, K.
- Venue
- Journal of Hematology & Oncology
- Published
- 2016-11-03
- Volume
- 9
- Issue
- 1
- Pages
- 116-116
- ISSN
- 1756-8722 (ISSN-L)
- OpenAlex
- W2548238752
- Cited by
- 319
- References
- 55
- FWCI
- 12.11
- Type
- journal article
- Language
- en
- Open access
- gold
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- Zelle-Rieser, C., Thangavadivel, S., Biedermann, R., Brunner, A., Stoitzner, P., Willenbacher, E., Greil, R., & Jöhrer, K. (2016). T cells in multiple myeloma display features of exhaustion and senescence at the tumor site. Journal of Hematology & Oncology. https://doi.org/10.1186/s13045-016-0345-3
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